Necrosis, Apoptosis, and Postmortem Changes Flashcards
(38 cards)
1
Q
Liver
A
Normal liver sinks, diseased liver with hepatic lipidosis floats
2
Q
Necrosis
A
- Death by swelling of the cell with eventual rupture of cell membranes
- Common usage - cell death + degradative changes
- -Typically involves groups or zones of cells and elicits an inflammatory response
3
Q
Apoptosis
A
- In contrast to necrosis, is directed by cellular signaling cascades and typically affects individual cells
- Process of condensation and shrinkage of the cell and its organelles with eventual fragmentation of the cell
4
Q
Autophagy
A
-A possible third mechanism of cell death
5
Q
Autolysis
A
=”Self-digestion”
- Degradative changes in a cell due to action of endogenous enzymes, primarily from lysosomes
- Changes are amplified and accelerated by bacterial decomposition from bacteria
- Putrefaction
6
Q
Putrefaction
A
=Postmortem bacterial metabolism and dissolution of host tissues result in the production of color and texture changes, gas production, and odors
7
Q
Fixation
A
- Rapid killing of cells by denaturing proteins to prevent autolysis and preserve architecture
- Commonly use 10% neutral buffered formalin
8
Q
Morphologic alterations in cell injury
A
- Reversible injury
- Irreversible injury
9
Q
Reversible injury
A
- Generalized cell swelling and swelling of its organelles, blebbing of the plasma membrane, detachment of ribosomes from the ER and clumping of nuclear chromatin
- Within limits, the cell can repair these derangements
10
Q
Irreversible injury
A
- Persisent or excessive injury causes cells to pass the “point of no return” into irreversible injury and cell death
- Different injurious stimuli may induce death by necrosis or apoptosis
11
Q
Morphologic changes associated with necrosis
A
- Color change
- -Pallor diffuse or patchy
- -Dark red, brown or black
- Loss of strength
- Odor
- -Foul odor if putrefactive bacteria present
12
Q
Histologic features of single cell necrosis
A
- Necrotic cells unable to maintain membrane integrity - contents often leak out, inciting inflammation
- Histologically:
- -Increased eosinophilia in HE stained slides due to decreased RNA
- -Glassy homogeneous appearance due to loss of glycogen particles
- -Vacuolated (moth-eaten) cytoplasm due to enzymes digesting organelles
- -Three nuclear patterns, all due to breakdown of DNA:
- –Karyolysis
- –Pyknosis
- –Karyorrhexis
13
Q
Irreversible cell injury morphology
A
- Karyolysis
- Pyknosis
- Karyorrhexis
14
Q
Karyolysis
A
=Basophilia of the chromatin fades due to loss of DNA
–Chromatin dissolution due to action of DNAases and RNAases
15
Q
Pyknosis
A
=Nuclear shrinkage and increased basophilia
–Also seen in apoptotic cell death
16
Q
Karyorrhexis
A
=Pyknotic nucleus undergoes fragmentation
17
Q
Morphologic changes in reversible cell injury and necrosis
A
- Normal kidney tubules with viable epithelial cells
- Early (reversible) ischemic injury showing surface blebs, increased eosinophilia of cytoplasm, and swelling of occasional cells
- Necrosis (irreversible injury) of epithelial cells, with loss of nuclei, fragmentation of cells, and leakage of contents
18
Q
Advanced cellular changes
A
- Loss of cell outline
- Loss of differential staining
- Absence of cells
19
Q
Possible sequelae to necrosis
A
- Death
- Inflammation
- Liquefaction (loses structure)
- Encapsulation (collagen capsule formation)
- Sequestration (sequestrum = fragment of dead, isolated tissue)
- Sloughing (ulcer = surface excavation due to sloughing of necrotic tissue; tissue extends below the basal layer of epithelium)
- Mineralization
- Healing: outcome depends on the type of tissue and extent of injury
20
Q
Apoptosis
A
- Pathway of cell death that is tightly regulated by intrinsic enzymes (degrade own DNA)
- Apoptotic bodies: portions of the cytoplasm and nucleus of the apoptotic cell
- -Plasma membrane remains intact, but its structure is altered so that phagocytosis is stimulated quickly
- -Cell fragments are rapidly devoured before the contents have leaked out - no inflammation
21
Q
Apoptosis physiological situations
A
- Embryogenesis
- Involution of hormone-dependent tissues
- Elimination of potentially harmful self-reactive lymphocytes
- Death of host cells that have served their useful purpose (ex: neutrophils)
22
Q
Apoptosis pathologic conditions
A
- DNA damage (radiation, cytotoxic cancer drugs)
- Accumulation of misfolded proteins (degenerative diseases of the CNS)
- Cell death in certain infections (simian immunodeficiency virus - SIV)
- Pathologic atrophy in parenchymal organs after duct obstruction (pancreas, parotid gland, kidney)
23
Q
Apoptosis morphology
A
- Cell shrinkage
- Chromatin condensation (aggregates peripherally, under the nuclear membrane)
- Cytoplasmic blebs and apoptotic bodies
- Phagocytosis of apoptotic bodies, usually by macrophages
24
Q
Mechanisms of apoptosis
A
-Activated caspases
25
Caspases
Proteases that exist as inactive proenzymes (zymogens) in the cytoplasm
26
Two distinct pathways of apoptosis that converge on caspase activation
1. Intrinsic mitochondrial pathway
2. Extrinsic death receptor pathway
-Differ in induction and regulation of apoptosis
27
Intrinsic mitochondrial pathway
- Can be triggered by a variety of cell stressors
- Mitochondrial outer membrane permeability (MOMP) is increased due to signaling from BCL2 family proteins
- Cytochrome-c and other pro-apoptotic proteins leak out of the mitochondrial intermembrane space and into the cytosol
- Cytochrome-c promotes the assembly of the apoptosome
- Apoptosome activates caspases
* Note: MOMP is the lethal permeabilization that initiates intrinsic apoptosis, NOT mitochondrial permeability transition pore
28
Extrinsic death receptor pathway
- Plasma membrane receptors are activated
- Lead to the assembly of adaptor proteins into a "death inducing signaling complex" which activates caspases
- Death receptors: Fas-receptor (TNF family of receptors)
29
Postmortem change
"Decomposition"
=Degradative changes seen in cells, tissues, and organs after death of the animal
--These changes are due to the action of lysosomal enzymes
30
Postmortem change microscopic alterations
- Uniform loss of differential staining in a tissue section
- Bacilli in blood vessels and tissues without inflammation
- Gas bubbles - from putrefactive bacteria
- Hemolysis of red blood cells - appear faint pink or orange, with indistinct margins
- Desquamation of endothelium and epithelium (usually with normal morphology)
31
Postmortem change gross alterations
- Postmortem tymapnities ("bloat")
- -Distension of GIT; prolapsed rectum or vagina
- Postmortem emphysema
- -Gas pockets in tissues
- -Due to gas-producing, PM bacilli
- Epithelial desquamation - esp. in rumen
- Rigor mortis
- Algor mortis
- Liver mortis
- Postmortem clotting
- Hemoglobin imbibition
- Bile imbibition
- Pseudomelanosis
32
Rigor mortis
- Stiffening of muscles after death
- Due to release of Ca2+ and decreased ATP --> muscle contraction
- 1-6 hours after death
33
Algor mortis
-Cooling of body after death
34
Liver mortis
- Hypostatic congestion
- Dark discoloration of dependent tissues
- Due to gravitation of blood
35
Postmortem clotting
- Clotting of heart and vessels usually occurs within several hours
- Before the clot forms, erythrocytes may settle resulting in a clot having two separate portions
- -A red and yellow clot --> chicken fat clot
- Separation depends on the erythrocyte sedimentation rate (ESR) and is normally high in horses
- PM clots: unattached and tend to be shiny and wet and form a perfect cast of vessel lumen
- AM clots: attached to vessel walls, tend to be dry and dull, and are laminated with a tail extending downstream from the point of attachment
36
Hemoglobin imbibition
-Postmortem hemolysis --> diffusion of hemoglobin into intima and surrounding tissues --> pink or red discoloration
37
Bile imbibition
-Yellow-green discoloration
38
Pseudomelanosis
-Hydrogen sulfide produced by intestinal bacteria + iron from hemolyzed RBC --> iron-sulfide
